Posttraumatic stress disorder (PTSD) is a prevalent, debilitating psychiatric disorder. Only two types of treatment have shown efficacy for chronic PTSD in replicated research: exposure-based cognitive behavioral therapies (CBT) and serotonin reuptake inhibitors. Cognitive behavioral therapies, which focus on re-exposure to traumatic memories and reminders to promote processing, have strong theoretical and empirical foundations. Yet multiple studies also document a central role for social and interpersonal processes in recovery after trauma. PTSD treatment research has not attempted to test these mechanisms. Interpersonal Psychotherapy (IPT), a well established, efficacious treatment for mood disorders, differs in theory and technique from CBT despite equal efficacy. Our pilot study found IPT to have great promise for PTSD, warranting a controlled trial. Unlike CBT treatments for PTSD, IPT targets interpersonal functioning, encouraging neither re-experiencing of traumatic memories nor out-of-session exposure to reminders of the trauma. Although exposure-based treatments are generally considered superior for anxiety disorders, PTSD is a hybrid disorder with features of both affective and anxiety disorders. IPT is thus a plausible alternative treatment approach to PTSD. Our group conjoins experience in randomized clinical trials (RCTs), in IPT and PE research, in psychosocial treatments for PTSD, and in cultural approaches to psychotherapy. We propose to test the efficacy of IPT for PTSD under controlled conditions. A 14-week RCT will compare IPT adapted for PTSD (IPT-PTSD), Prolonged Exposure (PE) therapy as a reference treatment, and Relaxation therapy (R) as a control treatment for 165 patients with chronic PTSD. Independent evaluators will assess outcomes. Responders will enter a three-month observational follow-up phase to assess persistence of treatment benefits. This design has been recently recommended in medicine to test new drugs being introduced for conditions with already established treatments. This state-of-the-art design will allow clinicians to interpret results with practicality. It presents a relatively rare and nearly ideal opportunity to study psychotherapy mechanisms by contrasting two very different treatments. The study will explore hypotheses about treatment mechanism by studying the timing of exposure-related change and interpersonal change in the two active treatments. In response to helpful comments from reviewers, we have standardized lengths of treatment, bolstered statistical analyses, and increased sample size among other adjustments for this final submission.